Difluorobutenes and difluorobutanes

ABSTRACT

A process for the preparation of a compound of formula (I): 
     
         HetSCH.sub.2 CH.sub.2 CH═CF.sub.2                      (I) 
    
     wherein Het is an optionally substituted 5- or 6-membered heterocyclic ring, which comprises reacting a compound of formula (II): 
     
         HetSH                                                      (II) 
    
     with a compound of formula (III): 
     
         CF.sub.2 ═CHCH.sub.2 CH.sub.2 L                        (III) 
    
     wherein L is chlorine or bromine or a group --OSO2R a  wherein R a  is a C1-4 alkyl group or a phenyl group optionally substituted by a C1-4 alkyl group.

This application is a division of application Ser. No. 08/286,142, filedAug. 4, 1994 now U.S. Pat. No. 5,728,833.

This invention relates to a chemical process for the preparation ofcompounds useful as nematicides, and to intermediates of use in theprocess.

According to the present invention there is provided a process for thepreparation of a compound of formula (I):

    HetSCH2CH2CH═CF2                                       (I)

wherein Het is an optionally substituted 5- or 6-membered heterocyclicring, which comprises reacting a compound of formula (II):

    HetSH                                                      (II)

with a compound of formula (III):

    CF2═CHCH2CH2L                                          (III)

wherein L is chlorine or bromine or a group --OSO2R^(a) wherein R^(a) isa C1-4 alkyl group or a phenyl group optionally substituted by a C1-4alkyl group.

The 5- or 6-membered heterocyclic ring may be for example an oxazole,isoxazole, thiazole, isothiazole, imidazole, 1,2,4- or 1,3,4-oxadiazole,1,2,4- or 1,3,4-thiadiazole, pyridine, pyridazine, pyrimidine, orpyrazine ring, or, except in the case of oxadiazoles or thiadiazoles, abenz derivative of any of these heterocyclic rings. The optionalsubstituents may comprise one or more aliphatic or alicyclic radicals of1 to 8 or more carbon atoms, for example alkyl, alkenyl, or alkynylradicals of 1 to 6 carbon atoms, cycloalkyl and cycloalkyl radicals;halogen; haloalkyl; haloalkenyl; alkoxy; alkenoxy; alkoxyalkyl;haloalkoxy; haloalkenoxy; alkylthio; haloalkylthio; cyano; nitro; amino;amino substituted with one or two alkyl groups each having one to threecarbon atoms; hydroxy; acylamino; carboxy or aliphatic ester thereofhaving one to six or more carbon atoms; or carbamoyl optionallysubstituted with one or two alkyl groups each having from one to sixcarbon atoms, or by a polymethylene di-radical forming, with thenitrogen atom of the carbamoyl group, a 5- or 6-membered ring.

According to one aspect, the present invention provides a process forthe preparation of a compound of formula (IV) wherein X is O or S, R¹,R², R³, and R⁴ are independently hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, alkylcycloalkyl, halogen, haloalkyl, haloalkenyl, alkoxy,alkenoxy, alkoxyalkyl, haloalkoxy, haloalkenoxy, alkylthio,haloalkylthio, cyano, nitro, amino, NR⁵ R⁶, hydroxy, amino, acylamino,--CO₂ R⁷, CONR⁶ R⁷ ; or R¹ and R² when taken together form a 5- or6-membered ring; R⁶ and R⁷ are hydrogen or C₁₋₄ alkyl; R⁵ is C₁₋₄ alkyl,which comprises reaction of a compound of formula (V) with a compound offormula (VI) wherein R^(a) is a C₁₋₄ alkyl group or a phenyl groupoptionally substituted with a C₁₋₄ alkyl group.

When any of R¹ to R⁴ is an alkyl group it can be straight or branchedchain and is preferably C₁₋₄ alkyl, in particular, methyl, ethyl,propyl, isopropyl, n-butyl, iso-butyl, sec-butyl or tertiary butyl.

When any of R¹ to R⁴ is an alkenyl or alkynyl group it can be straightor branched chain and preferably contains up to 6 carbon atoms, forexample, allyl or propargyl.

When any of R¹ to R⁴ is a cycloalkyl or alkylcycloalkyl group, itpreferably contains from 3 to 7 carbon atoms, for example, cyclopropyl,cyclopentyl, cyclohexyl or methylcyclopropyl.

When any of R¹ to R⁴ is halogen, it is preferably fluorine, chlorine orbromine.

When any of R¹ to R⁴ is a haloalkyl or haloalkenyl group, the halogen ispreferably chlorine, fluorine or bromine, the alkyl moiety is preferablyC₁₋₄ alkyl, for example, trifluoromethyl, trifluoroethyl orpentafluoroethyl and the alkenyl is preferably C₂₋₆ alkenyl.

When any of R¹ to R⁴ is an alkoxy, alkenoxy or alkoxyalkyl group it canbe straight or branched chain and preferably contains up to 6 carbonatoms, for example, a methoxy, ethoxy, propoxy, butoxy, butenoxy,methoxymethyl, methoxyethyl or ethoxymethyl group.

When any of R¹ to R⁴ is a haloalkoxy group, it can be straight orbranched chain and preferably contains up to 6 carbon atoms. The halogenis preferably chlorine, fluorine or bromine. Particular examples aretrifluoromethoxy, trifluoroethoxy or pentafluoroethoxy.

When any of R¹ to R⁴ is a haloalkenoxy group, it can be straight orbranched chain and preferably contains up to 6 carbon atoms. The halogenis preferably chlorine, fluorine or bromine. Particular examples areOCH₂ CH₂ CH═CF₂ and OCH₂ CH₂ CH═CHF.

When any of R¹ to R⁴ is an alkylthio group, the alkyl preferablycontains up to 4 carbon atoms. For example, --S-methyl, --S-ethyl,--S-propyl, S-butyl.

When any of R¹ to R⁴ is an haloalkylthio group, the alkyl preferablycontains up to 4 carbon atoms, and the halogen group is preferably,fluorine, chlorine or bromine, for example, --S--CF₃, --S--C₂ H₄ F,--S(CH₂)₂ CH₂ F, SCBrF₂, SCClF₂ and --S--CH₂ CF₃.

When any of R¹ to R⁴ is NR⁵ R⁶, it is preferably NHCH₃, N(CH₃)₂ or N(C₂H₅)₂.

When any of R¹ to R⁴ is acylamino, it is preferably NHCOCH₃ or NHCOC₂H₅.

When any of R¹ to R⁴ is CO₂ R⁷, R⁷ is preferably hydrogen, methyl orethyl.

When any of R¹ to R⁴ is CONR⁵ R⁷, R⁵ and R⁷ are preferably hydrogen,methyl or ethyl. Especially preferred is CONH₂.

When R¹ and R² are taken together to form a 5- or 6-membered ring, it ispreferably a carbocylic ring, for example, --(CH₂)₃ --, --(CH₂)₄ -- or--CH═CH--CH═CH--.

Of particular interest are compounds of formula (I) where X is O or S,and R¹ to R⁴ are independently hydrogen, fluorine, chlorine, methyl,ethyl, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy,trifluoroethoxy, SCH₃ and SCH₂ CF₃.

The nematicidal properties of compounds of formula (IV) and oxidisedderivatives thereof are described in published UK Patent Application No.2,270,689A.

Examples of the compounds of formula (IV) which may be preparedaccording to the process of the invention are set out in Table I.

                  TABLE I    ______________________________________    COM-    POUND    NO.    R.sup.1    R.sup.2    R.sup.3  R.sup.4                                               X    ______________________________________    1      H          H          H        H    S    2      H          H          H        H    O    3      H          F          H        H    O    5      NO.sub.2   H          H        H    O    6      NH.sub.2   H          H        H    O    7      CH.sub.3   H          H        H    S    8      H          F          F        H    O    10     CO.sub.2 CH.sub.3                      H          H        H    O    11     NHCOCH.sub.3                      H          H        H    S    12     H          H          H        H    S    13     COOH       H          H        H    S    15     F          H          H        H    S    16     H          H          H        CH.sub.3                                               S    17     H          H          CH.sub.3 H    O    18     H          H          CH.sub.2 CH═CH.sub.2                                          H    O    19     H          H          .sup.c C.sub.3 H.sub.5                                          H    O    20     H          H          Cl       H    O    21     H          H          CN       H    S    22     H          CH.sub.3   H        H    S    23     H          CH.sub.2 CH═CH.sub.2                                 H        H    O    24     H          .sup.c C.sub.3 H.sub.5                                 H        H    O    26     H          C.sub.6 H.sub.5                                 H        H    O    27     CH.sub.3   CH.sub.3   H        H    O    28     Cl         Cl         H        H    S    29     F          Cl         H        H    O    30     OCH.sub.3  H          NHCOCH.sub.3                                          H    O    31     OCH.sub.3  H          OCH.sub.3                                          H    O    32     OCH.sub.3  OCH.sub.3  H        H    O    33     1-CH.sub.3 --.sup.c C.sub.3 H.sub.5                      H          H        H    S    34     OH         F          H        H    O    35     OH         H          Cl       H    S    36     H          H          CO.sub.2 CH.sub.3                                          H    O    37     OCH.sub.2 CF.sub.3                      H          H        H    S    40     H          H          CH.sub.2 OCH.sub.3                                          H    S    41     H          CH.sub.3   H        H    O    42     H          H          CN       H    O    43     --CH═CH--CH═CH--                             H          H    S    44     --CH═CH--CH═CH--                             H          H    O    ______________________________________     .sup.c indicates a cyclic substituent

According to the process of the invention, a compound of Formula (V)wherein R¹, R², R³, R⁴, and X have any of the meanings given above, isreacted with a compound of Formula (VI) wherein R^(a) is a C₁₋₄ alkylgroup, especially methyl, or a phenyl group optionally substituted witha C₁₋₄ alkyl group, especially para-tolyl, under conditions well knownin the art for such displacement reactions, for example in the presenceof a mild base such as an alkali metal carbonate, for example potassiumor sodium carbonate, in an inert solvent, at a temperature in the rangefrom 40° C. to 100° C., and most conveniently at the reflux temperatureof a suitable inert solvent such as acetone which has a boiling pointwithin this range.

Compounds of Formula (VI) may be prepared by the following sequence ofreactions. Hydrogen bromide is reacted with the commercially availablecompound of Formula (VII) under standard conditions for an additionreaction, for example by passing hydrogen bromide gas through a solutionof the compound of Formula (VII) in an inert solvent to give thecompound of Formula (VIII). The compound of Formula (VIII) is thenreacted with the silver salt of a sulphonic acid of Formula R^(a) SO₃ H,wherein R^(a) has the meaning given above, for example the silver saltof 4-methylbenzenesulphonic acid (silver tosylate) or the silver salt ofmethanesulphonic acid (silver mesylate), preferably in an inert solventin the absence of light, to give the corresponding compound of Formula(IX). Debromofluorination of the compound of Formula (IX), for exampleby reaction with zinc, preferably in the presence of a suitable catalystsuch as iodine, gives the compound (VI), wherein R^(a) has the meaningsgiven above.

It will be appreciated by those skilled in the art that compounds ofFormula (V) exist in tautomeric equilibrium between the equivalent2-mercapto and 2-thione forms. For the sake of convenience, thecompounds are referred to herein in their 2-mercapto form unlessotherwise stated.

Compounds of Formula (V) are commercially available or may be preparedfrom commercially available precursors by standard procedures well knownin the art. Typical procedures suitable for the preparation of many ofthe relevant compounds of Formula (V) and their precursors may be foundin the following standard references: Comprehensive HeterocyclicChemistry (Published by Pergamon, Edited by Katritzky and Rees), 1984,e.g. pages 177-331; Journal of Organic Chemistry, 19, 758-766 (1954);Heterocyclic Compounds (Published by Wiley, Edited by Elderfield),Volume 5; Organic Compounds of Sulphur, Selenium and Tellurium(Published by The Chemical Society, Specialist Reports), Volumes 3, 4and 5; Warburton et al, Chemical Reviews, 57, 1011-1020 (1957). By wayof example, many of the compounds of formula (V) where X is oxygen maybe prepared by reacting a correspondingly substituted 2-aminophenol or asalt thereof, with thiophosgene, in an inert solvent such as diethylether or chloroform, and optionally in the presence of a base, such aspotassium carbonate, and/or water. Also by way of example, many of thecompounds of formula (V) where X is sulphur may be prepared by the HerzReaction (Warburton et al, Chemical Reviews, 57, 1011-1020 (1957)) inwhich appropriately substituted anilines are reacted sequentially withdisulphur dichloride and aqueous sodium hydroxide to produce thecorresponding 2-mercapto aniline derivative, which is then reacted withcarbon disulphide to produce the 2-mercaptobenzthiazole of formula (V).Benzthiazoles of formula (V) may also be prepared from appropriatelysubstituted N-phenylthioureas by oxidation (for example in the presenceof molecular bromine) and replacement of the amino group of theresulting 2-aminobenzthiazole with a 2-mercapto group by reaction with abase and carbon disulphide or by diazotisation, reaction with a halideand displacement of the 2-halo group using NaSH or thiourea.N-phenylthioureas are available by reaction of the correspondinganilines with ammonium thiocyanate. Compounds of Formula (V) may also beprepared by reaction of the correspondingly substituted2-halonitrobenzene by reaction with sodium sulphide, sulphur (S₈), andcarbon disulphide, or by reaction of the correspondingly substitutedphenyl isothiocyanate with sulphur (S₈) to produce the correspondingmercaptobenzthiazole. All of these reactions are well documented in thechemical literature. The choice of the appropriate procedure will dependupon the particular nuclear substitution pattern required and is withinthe normal skill of the art.

A general procedure for the preparation of 2-mercaptobenzthiazoles (fromthe corresponding 2-aminobenzthiazoles) is illustrated by the followingpreparation of 6-fluoro-2-mercaptobenzthiazole (Ref. J.Het. Chem. (1980)17 1325).

A solution of 2-amino-6-fluorobenzthiazole (10.0 g) in water (100 cm³)containing sodium hydroxide (50.0 g) was stirred and heated to refluxfor 18 hours, cooled to the ambient temperature and filtered. Carbondisulphide (17.5 cm³) was added to the filtrate and the mixture washeated to reflux for 4 hours, cooled to the ambient temperature, dilutedwith water and neutralised with acetic acid. The fawn solid whichprecipitated was filtered from solution, washed with water and dried bysuction to give the title product, mp above 260° C., M⁺ =185.

The following compounds were prepared using the above method.

(i) 2-Mercapto-4-methylbenzthiazole: mp above 260° C.; M⁺ =181; yellowsolid

(ii) 2-Mercapto-6-methylbenzthiazole: mp 248° C.; M⁺ =181; yellow solid

A general procedure for the preparation of 2-mercaptobenzoxazoles (fromthe corresponding 2-aminophenol) is illustrated by the followingpreparation of 2-mercapto-5-methylbenzoxazole.

To a brown solution of 2-amino-5-methylphenol (5 g) in 2 M NaOH (80 cm³)stirring at the ambient temperature was added carbon disulphide and thereaction mixture was stirred for 5 days. The solution was acidified topH 4 by the addition of concentrated hydrochloric acid, causingformation of a beige precipitate. The precipitate was filtered and driedby suction to give the title product as a free flowing beige powder(4.06 g). ¹ H NMR (DMSO): δ 13.9 (1H,br s); 7.5(1H,d); 7.18(1H,d);7.15(1H,s); 2.49(3H,s) ppm.

According to a further aspect of the present invention there is provideda process for the preparation of a compound of formula (X) wherein R⁸,R⁹, R¹⁰ and R¹¹ are independently hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, alkylcycloalkyl, halogen, haloalkyl, haloalkenyl, alkoxy,alkenoxy, alkoxyalkyl, haloalkoxy, haloalkenoxy, alkylthio,haloalkylthio, --SCH2CH2CH═CF2, cyano, nitro, amino, NR12R13, hydroxy,acylamino, --CO2R¹⁴, --O(CH2)mCO2R14, CONR13R14, phenyl, phenoxy, benzylor benzyloxy, the phenyl group or phenyl moiety of the benzyl groupbeing optionally substituted in the ring; or R⁹ and R¹⁰ when takentogether form a 5- or 6-membered ring; m is 1 or 2; R¹³ and R¹⁴ arehydrogen or C₁₋₄ alkyl; R¹¹ is C₁₋₄ alkyl; provided that at least one ofR8 to R11 is SCH2CH2CH═CF2, which comprises reaction of a compound offormula (XI) with a compound of formula (VI) wherein R^(a) is a C₁₋₄alkyl group or a phenyl group optionally substituted with a C1-4 alkylgroup.

When any of R⁸ to R¹¹ is an alkyl group it can be straight or branchedchain and is preferably C₁₋₄ alkyl, in particular ethyl, propyl,isopropyl, n-butyl, iso-butyl, sec-butyl or tertiary butyl.

When any of R⁸ to R¹¹ is an alkenyl or alkynyl group it can be straightor branched chain and preferably contains up to 6 carbon atoms, forexample, allyl or propargyl.

When any of R⁸ to R¹¹ is a phenyl, phenoxy, benzyl or benzyloxy group,the phenyl moiety may be optionally substituted with halogen, (forexample, chlorine, fluorine, or bromine), cyano, alkyl, haloalkyl,alkoxy or haloalkoxy, the alkyl group being preferably C₁₋₄ alkyl andthe alkoxy group being preferably C₁₋₆ alkyl. Examples of such groupsare 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-chlorophenyl, 2,4- or 2,6-difluorophenyl, 2,4- or 2,6- dichlorophenyl, 2-chloro-4-fluorophenyl,2-chloro-6-fluorophenyl, 2-fluoro-4-chlorophenyl,2-fluoro-6-chlorophenyl, 2-,3- or 4-methoxyphenyl, 2, 4-dimethoxyphenyl,2-, 3-, or 4-ethoxyphenyl, 2-, 3- or 4-methylphenyl, 2-, 3- or4-ethylphenyl, 2-, 3- or 4-trifluoromethylphenyl, and the correspondingring substituted benzyl, phenoxy and benzyloxy groups.

When any of R⁸ to R¹¹ is a cycloalkyl or alkylcycloalkyl group, itpreferably contains from 3 to 7 carbon atoms, for example, cyclopropyl,cyclopentyl, cyclohexyl or methylcyclopropyl.

When any of R⁸ to R¹¹ is halogen, it is preferably fluorine, chlorine orbromine.

When any of R⁸ to R¹¹ is haloalkyl, the halogen is preferably chlorine,fluorine or bromine, the alkyl moiety is preferably C₁₋₄ alkyl, forexample, trifluoromethyl, trifluoroethyl or pentafluoroethyl, and thealkenyl moiety is preferably C₂₋₆ alkenyl.

When any of R⁸ to R¹¹ is an alkoxy, alkenoxy or alkoxyalkyl group, itcan be straight or branched chain and preferably contains up to 6 carbonatoms, for example, methoxy, ethoxy, propoxy, butoxy, butenoxy,methoxymethyl, methoxyethyl or ethoxymethyl.

When any of R⁸ to R¹¹ is a haloalkoxy group, it can be straight orbranched chain and preferably contains up to 6 carbon atoms. The halogenis preferably chlorine, fluorine or bromine. Particular examples aretrifluoromethoxy, trifluoroethoxy and pentafluoroethoxy.

When any of R⁸ to R¹¹ is a haloalkenoxy group, it can be straight orbranched chain and preferably contains up to 6 carbon atoms. The halogenis preferably chlorine, fluorine or bromine. Particular examples areOCH₂ CH₂ CH═CF₂ and OCH₂ CH₂ CH═CHF.

When any of R⁸ to R¹¹ is an alkylthio group, the alkyl preferablycontains up to 4 carbon atoms. For example, --S-methyl, --S-ethyl,--S-propyl, S-butyl.

When any of R⁸ to R¹¹ is a haloalkylthio group, the alkyl preferablycontains up to 4 carbon atoms, i.e. methyl, ethyl, propyl and butyl. Thehalogen group is preferably, fluorine, chlorine or bromine, for example,--S--CF3, --SC2H4F, --S(CH2)2CH2F, SCBrF2, SCClF2 and S--CH2CF3.

When any of R⁸ to R¹¹ is --SCH₂ CH₂ CH═CF₂ it is preferably asubstituent in the R⁸ or R¹¹ position, or alternatively, in both the R⁸and R¹¹ positions or in both the R⁸ and R¹⁰ positions.

When any of R⁸ to R¹¹ is NR¹² R¹³, it is preferably NHCH₃, N(CH₃)₂ orN(C₂ H₅)₂.

When any of R⁸ to R¹¹ is acylamino, it is preferably NHCOCH₃ or NHCOC₂H₅.

When any of R⁸ to R¹¹ is CO₂ R¹⁴, R¹⁴ is preferably hydrogen, methyl orethyl.

When any of R⁸ to R¹¹ is O(CH₂)_(m) CO₂ R¹⁴, m is preferably 2 and R¹⁴is preferably hydrogen, methyl or ethyl.

When any of R⁸ to R¹¹ is CONR¹³ R¹⁴, R¹³ and R¹⁴ are preferablyhydrogen, methyl or ethyl. Especially preferred is CONH₂.

When R⁹ and R¹⁰ are taken together to form a 5- or 6-membered ring, itis preferably a carbocylic ring, for example, --(CH₂)₃ --, --(CH₂)₄ --or --CH═CH--CH═CH--.

Of particular interest are the compounds of formula (X) where R⁸ isselected from C₁₋₄ alkyl, C₁₋₄ haloalkyl, halogen, C₁₋₆ alkoxy orhydroxy, R⁹ is selected from hydrogen or C₁₋₄ alkyl, R¹⁰ is selectedfrom hydrogen, C₁₋₄ alkyl, C₁₋₆ alkoxy, hydroxy or halogen and R¹¹ isSCH₂ CH₂ CH═CF₂. Or alternatively, the compounds of formula (IX) whereR⁸ is phenyl, phenoxy, benzyl or benzyloxy, the phenyl group or phenylmoiety of the benzyl group being optionally substituted, R⁹ is hydrogenor C₁₋₄ alkyl, R¹⁰ is selected from hydrogen, C₁₋₄ alkyl, C₁₋₆ alkoxy,hydroxy or halogen and R¹¹ is --SCH₂ CH₂ CH═CF₂.

Also of particular interest are the compounds of formula (X) where R⁸ isSCH₂ CH₂ CH═CF₂, R⁹ is selected from hydrogen and C₁₋₄ alkyl, R¹⁰ isselected from hydrogen, C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₆ alkoxy, C₁ 6haloalkoxy, R¹¹ is selected from hydrogen, C₁₋₄ alkyl and optionallysubstituted phenyl.

The nematicidal properties of compounds of formula (X) and oxidisedderivatives thereof are described in published UK Patent Application No.2,270,688A.

Examples of the compounds of formula (X) which may be prepared accordingto the process of the invention are set out in Table II.

                                      TABLE II    __________________________________________________________________________    COMPOUND NO.             R.sup.8   R.sup.9                            R.sup.10 R.sup.11    __________________________________________________________________________    2.1      H         H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.3      CF.sub.3  H    OCH.sub.3                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.4      C.sub.6 H.sub.5                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.5      SCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    H        H    2.6      OC.sub.2 H.sub.5                       CH.sub.3                            H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.7      OCH.sub.3 H    n-C.sub.3 H.sub.7                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.9      OC.sub.3 H.sub.9                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.10     OCH.sub.2 CH═CHCH.sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.11     OH        H    n-C.sub.3 H.sub.7                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.12     CF.sub.3  H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.13     SCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    OCH.sub.2 CF.sub.3                                     H    2.14     CH.sub.3  H    OCH.sub.2 CH.sub.3                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.15     Cl        H    n-C.sub.3 H.sub.7                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.16     OCH.sub.2 C.sub.6 H.sub.5                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.17     OCH.sub.2 CO.sub.2 CH.sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.18     n-C.sub.3 H.sub.7                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.19     OCH.sub.2 (4-Cl--C.sub.6 H.sub.4)                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.20     OCH.sub.2 CO.sub.2 H                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.21     OCH.sub.2 CF.sub.3                       H    CH(CH.sub.3).sub.2                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.22     Cl        H    CH(CH.sub.3).sub.2                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.23     O(CH.sub.2).sub.2 CO.sub.2 CH.sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.24     OCH.sub.3 H    CH(CH.sub.3).sub.2                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.25     CH(CH.sub.3).sub.2                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.26     SCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    CH.sub.3 C.sub.6 H.sub.5    2.27     SCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    H        CH.sub.3    2.28     OCH.sub.3 --(CH.sub.2).sub.4 --                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.29     CH.sub.3  H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.30     CH.sub.3  H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.31     H         C(CH.sub.3).sub.3                            H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.32     H         CF.sub.3                            H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.33     H         CH(CH.sub.3).sub.2                            H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.34     H         Cl   H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.35     H         C.sub.6 H.sub.5                            H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.36     SCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.37     OCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.38     H         --(CH.sub.2).sub.3 --                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.39     CH.sub.3  CH.sub.3                            CH.sub.3 SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.40     --SCH.sub.2 CH.sub.2 CH═CF.sub.2                       CH.sub.3                            SCH.sub.2 CH.sub.2 CH═CF.sub.2                                     H    2.41     --C.tbd.CH                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.42     CN        H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.43     4-F--C.sub.6 H.sub.4                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.44     4-F--C.sub.6 H.sub.4                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.45     4-CF.sub.3 --C.sub.6 H.sub.4 CH.sub.2                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.46     .sup.c C.sub.3 H.sub.5                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.47     1-CH.sub.3 --.sup.c C.sub.3 H.sub.5                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.48     CH.sub.2 CF.sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.49     OCH.sub.2 CF.sub.3                       H    Cl       SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.50     CH.sub.2 OCH.sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.51     Cl        H    Cl       SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.52     --SCH.sub.2 CH.sub.2 CH═CF.sub.2                       H    OCH.sub.2 CH.sub.2 CH═CF.sub.2                                     H    2.53     F         H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.54     SCH.sub.3 H    F        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.55     C(CH.sub.3).sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.56     C(CH.sub.3).sub.3                       H    H        SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.57     H         --CH═CH--CH═CH--                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    2.60     OH        --CH═CH--CH═CH--                                     SCH.sub.2 CH.sub.2 CH═CF.sub.2    __________________________________________________________________________     .sup.c indicates a cyclic substituent

According to the process of the invention, a compound of Formula (XI)wherein R⁸, R⁹, R¹⁰ and R¹¹ have any of the meanings given above isreacted with a compound of Formula (VI) wherein R^(a) is a C₁₋₄ alkylgroup, especially methyl, or a phenyl group optionally substituted witha C₁₋₄ alkyl group, especially para-tolyl, under conditions well knownin the art for such displacement reactions, for example in the presenceof a mild base such as an alkali metal carbonate, for example potassiumor sodium carbonate, in an inert solvent, at a temperature in the rangefrom 40° C. to 100° C., and most conveniently at the reflux temperatureof a suitable inert solvent such as acetone which has a boiling pointwithin this range.

It will be appreciated by those skilled in the art that compounds ofFormula (XI) exist in tautomeric equilibrium between the equivalentmercapto and thione forms. For the sake of convenience, the compoundsare referred to herein in their mercapto form unless otherwise stated.

Compounds of Formula (XI) are commercially available or may be preparedfrom commercially available precursors by standard procedures well knownin the art. Typical procedures for the preparation of the relevantcompounds of Formula (XI) and their precursors may be found in thefollowing standard references: The Pyrimidines, D J Brown (Published byWiley, 1962); The Chemistry of Heterocyclic Compounds, Vol 16,Supplement I and Supplement II (Edited by A Weissberger). The choice ofthe most suitable process is dependent upon the particular substitutionpattern required and will be readily determined by those skilled in theart from the standard methods.

A general two step procedure for the preparation of 4-aryl-, 4-alkyl-,or 4-alkoxyalkyl- 2-pyrimidinethiones from the corresponding methylketone is given by R F Abdulla and R S Brinkmeyer in Tetrahedron 35,1675 (1979). The following intermediate compounds were preparedaccording to this procedure. The starting materials were commerciallyavailable.

(a) 4-phenyl-2(1H)-pyrimidinethione. ¹ H NMR (DMSO): δ 3.5(1H, br s);7.58(1H,d); 7.60-7.78(3H,m); 8.24(1H,d); 8.30(2H,dd) (yellow solid).

(b) 4-(4-fluorophenyl)-2(1H)-pyrimidinethione. ¹ H NMR (DMSO): δ7.44-7.54(2H,m); 7.56(1H,d); 8.20(1H,d) 8.30-8.40(2H,m); 13.90(1H, br s)(yellow solid).

(c) 4-cyclopropyl-2(1H)-pyrimidinethione. ¹ H NMR (DMSO): δ1.12-1.28(4H,m); 2.12-2.24(1H,m); 6.90(1H,d); 7.98(1H,d) (orange solid).

(d) 4-(1-methylcyclopropyl)-2(1H)-pyrimidinethione. ¹ H NMR (DMSO): δ1.00-1.08(2H,m); 1.30-1.38(2H,m); 1.48(3H,s); 6.84(1H,d); 7.92(1H,d);13.54(1H,br s) (yellow solid).

In a further aspect, the invention provides a process of preparing acompound of formula (IV) as hereinbefore defined, which comprisesreaction of a compound of formula (V) as hereinbefore defined with4-bromo-1,1-difluorobut-1-ene.

In a still further aspect, the invention provides a process of preparinga compound of formula (X) as hereinbefore defined, which comprisesreaction of a compound of formula (XI) as hereinbefore defined with4-bromo-1,1-difluorobut-1-ene.

According to the last two foregoing aspects of the invention, a compoundof formula (V) as hereinbefore defined, or a compound of formula (XI) ashereinbefore defined, is reacted with 4-bromo-1,1-difluorobut-1-ene,under conditions well known in the art for such displacement reactions,for example in the presence of a mild base such as an alkali metalcarbonate, for example potassium or sodium carbonate, in an inertsolvent, at a temperature in the range from 40 to 100° C., and mostconveniently at the reflux temperature of a suitable inert solvent suchas acetone which has a boiling point within this range.

4-Bromo-1,1-difluorobut-1-ene may be prepared by the following sequenceof reactions: hydrogen bromide is reacted with the commerciallyavailable compound 4-bromo-1,1,2-trifluorobut-1-ene having the formula(VII), under standard conditions for an addition reaction, for exampleby passing hydrogen bromide gas through a solution of4-bromo-1,1,2-trifluorobut-1-ene in an inert solvent, optionally in thepresence of a free radical generator (e.g. benzoyl peroxide), to give1,4-dibromo-1,1,2-trifluorobutane (Formula VIII). This compound is thentreated with a debromofluorinating agent, which removes a bromine atomand a fluorine atom from the 1,4-dibromo-1,1,2-trifluorobutane to give4-bromo-1,1-difluorobut-1-ene. Examples of debromofluorinating agentsinclude zinc, magnesium, and aluminium. 4-Bromo-1,1-difluorobut-1-ene isa relatively volatile compound, and if the debromofluorination reactionis done in an organic solvent (e.g. acetone), in order to minimiselosses it may be preferable to react the solution of the productobtained from the bromodefluorination reaction directly with themercaptopyrimidine, mercaptobenzoxazole, or mercaptobenzthiazole, ratherthan to isolate and purify the 4-bromo-1,1-difluorobut-1-ene beforereacting it with the mercapto pyrimidine, mercaptobenzoxazole ormercaptobenzthiazole.

In an alternative procedure, the debromofluorination reaction may becarried out using water as the reaction medium. As before, zinc,aluminium, or magnesium may be used as the debromofluorinating agent.Mixtures of metals may also be used, for example magnesium with a smallproportion of zinc or aluminium. The 4-bromo-1,1-difluorobut-1-ene mayconveniently be recovered by distilling it from the reaction mixture, orby extracting it with a water-immiscible solvent according to standardprocedures.

In a further alternative procedure for preparing4-bromo-1,1-difluorobut-1-ene, 1,4-dibromo-1,1,2-trifluorobutane may bedebromofluorinated electrolytically, using for example an electrolyticcell containing a solution of a zinc salt (e.g. zinc chloride) andhaving a lead cathode and a carbon anode.

In this procedure, at the end of a period of electrolysis the contentsof the cathode compartment may be transferred to a distillationapparatus, the 4-bromo-1,1-difluorobut-1-ene distilled out andrecovered, and the catholyte transferred back to the cathode compartmentfor re-use. Compounds of Formulas (VI) and (IX) have not been previouslyreported. In two further aspects, therefore, the invention provides: acompound of Formula (VI) wherein R^(a) is a C₁₋₄ alkyl group or a phenylgroup optionally substituted with a C₁₋₄ alkyl group; and a compound ofFormula (IX) wherein R^(a) is a C₁₋₄ alkyl group or a phenyl groupoptionally substituted with a C₁₋₄ alkyl group. Preferred compounds ofFormula (VI) and (IX) for use in the process of the invention are thosein which R^(a) is methyl or para-tolyl, namely 4,4-difluorobut-3-enylmethanesulphonate, 4,4-difluorobut-3-enyl 4-methylbenzenesulphonate,4-bromo-3,4,4-trifluorobut-3-enyl methanesulphonate, and4-bromo-3,4,4-trifluorobut-3-enyl 4-methylbenzenesulphonate.

4-Bromo-1,1-difluorobut-1-ene has not previously been reported. Inanother aspect, therefore, the invention provides this compound, and theprocess of making it which comprises treating1,4-dibromo-1,1,2-trifluorobutane with a debromofluorinating agent.

The invention is illustrated by the following Examples in whichpercentages are by weight and the following abbreviations are used:gc=gas chromatography; nmr=nuclear magnetic resonance; s=singlet;d=doublet; t=triplet; q=quartet; m=multiplet; dd=double doublet;ddt=double doublet of triplets, dtd=double triplet of doublets; b orbr=broad; g=grammes; mg=milligrammes; CDCl₃ =deuterochloroform; Chemicalshifts (δ) are measured in parts per million from tetramethylene silane.CDCl₃ was used as solvent unless otherwise stated. M⁺ =molecular ion asdetermined by mass spectrometry; ir=infra red spectrometry; tlc=thinlayer chromatography; (dec)=decomposed on melting.

EXAMPLE 1

This example illustrates the preparation of1,4-dibromo-1,1,2-trifluorobutane.

A solution of 4-bromo-1,1,2-trifluorobut-1-ene (2.5 g) in drydichloromethane (25 cm³) at 0° C. was heated with HBr gas for 45minutes. The reaction mixture was then stirred at 0° C. for 1 hour. Thereaction mixture was made alkaline with 5% NaHCO₃ solution and extractedtwice with dichloromethane. The combined dichloromethane extracts weredried (MgSO₄), filtered and concentrated under reduced pressure to givea pale yellow liquid (2.84 g). The material was shown by gc analysis tobe greater than 99% pure. ¹ H NMR (CDCl₃): δ 4.75-5.07(1H,m);3.42-3.69(2H,m); 2.59-2.15(2H,m).

EXAMPLE 2

This Example illustrates the two step process for the preparation of4,4-difluorobut-3-enyl 4-methylbenzenesulphonate.

Step 1 4-Bromo-3,4,4-trifluorobutyl 4-methylbenzenesulphonate

To a stirred suspension of silver tosylate (1.03 g) in acetonitrile (10cm³) at the ambient temperature, protected from the light, was addeddropwise 1,4-dibromo-1,1,2-trifluorobutane. The reaction was then heatedunder reflux for 24 hours after which gc analysis indicated completeconsumption of starting material. The reaction mixture was cooled to theambient temperature and the precipitate was filtered off and washed withethyl acetate. The filtrate and ethyl acetate washings were combined andwashed with water and the aqueous layer extracted with ethyl acetate.The combined ethyl acetate layers were washed with water and brine,dried (MgSO₄) and evaporated under reduced pressure to give a brown oil(1.21 g). GC analysis showed this material to be >99% pure. ¹ H NMR(CDCl₃): δ 7.80(2H,d); 7.38(2H,d); 4.74(1H,m); 4.19(2H,m); 2.46(3H,s);2.20(2H,m).

Step 2 4,4-Difluorobut-3-enyl 4-methylbenzenesulphonate

To a stirred suspension of powdered zinc (1.41 g) and iodine (one grain)in methanol (3 cm³) was added a solution of 4-bromo-3,4,4-difluorobutyl4-methylbenzenesulphonate (710 mg) in methanol (2 cm³). The reactionmixture was refluxed for 21/2 hours after which gc analysis indicatedcomplete consumption of starting material. The organic phase waspipetted from the zinc suspension and the zinc was washed with 3portions of ethyl acetate. The combined ethyl acetate portions werewashed with 2 M hydrochloric acid, dried (MgSO₄) and evaporated underreduced pressure to give a brown liquid (470 mg). GC analysis showedthis material to be >99% pure. ¹ H NMR (CDCl₃): δ 7.79(2H,d);7.38(2H,d); 4.15(1H,m); 4.01(2H,m); 2.46(3H,s); 2.35(2H,m).

EXAMPLE 3

The general procedure according to the invention for the preparation of2-(4,4-difluorobut-3-enylthio)-substituted benzoxazoles andbenzthiazoles by reaction of the corresponding 2-mercapto heterocyclewith 4,4-difluorobut-3-enyl 4-methylbenzenesulphonate is illustrated bythe following preparation of 2-(4,4-Difluorobut-3-enylthio)benzoxazole(Compound No. 2).

2-Mercaptobenzoxazole (4.79 g) was added to a solution of1,1-difluorobut-1-en-4-yl 4-methylbenzenesulphonate (6.4 g) in acetone(200 cm³) containing potassium carbonate (5.06 g). The mixture washeated to reflux overnight (17 hr) and gc used to confirm that the1,1-difluorobut-1-en-4-yl 4-methylbenzenesulphonate had been consumedand the product had formed. The reaction mass was allowed to cool andwas filtered through a plug of High-Flo filter aid to remove insolubleinorganic material. The solid material was washed with ethyl acetate andthe combined organic portions evaporated under reduced pressure to give7.1 g of a brown oily residue. This material was fractionated by elutingthrough a bed of silica using hexane/ethyl acetate (40:1 by volume) assolvent to give the required product as a colourless oil (5.4 g, 92%based on the sulphonate); M⁺ =241; ¹ H NMR (CDCl₃): δ 2.5-2.6 (m 2H),3.3-3.4 (t 2H), 4.2-4.4 (m 1H), 7.2-7.35 (m 2H), 7.45 (dd 1H), 7.6 (dd1H).

EXAMPLE 4

The following compounds were prepared from the corresponding 2-mercaptobenzoxazole or 2-mercaptobenzthiazole using the method of Example 3.Where the 2-mercapto benzoxazoles and benzthiazoles are not readilyavailable commercially, they may be prepared by the standard proceduresdesired in the text, for example those illustrated below in Examples 5and 6.

(a) 2-(4,4-difluorobut-3-enylthio)-5-methylbenzoxazole (Compound No.41). ¹ H NMR (CDCl₃): δ 7.38(1H,s); 7.30(1H,d); 7.03(1H,d); 4.30(1H,m);3.32(2H,t); 2.69(2H,q); 2.45(3H,s); (oil).

(b) Methyl 2-(4,4-difluorobut-3-enylthio)benzoxazole-6-carboxylate(Compound No. 10). M⁺ =299; ¹ H NMR (CDCl₃): δ 2.5-2.6 (m 2H), 3.35 (t2H), 3.95 (s 3H), 4.2-4.4 (m 1H), 7.65 (d 1H), 8.05 (dd 1H), 8.15 (d1H); (oil).

(c) 2-(4,4-Difluorobut-3-enylthio)-6-nitrobenzoxazole (Compound No. 5).M⁺ =286; ¹ H NMR (CDCl₃): δ 2.55-2.65 (m 2H), 3.35-3.45 (t 2H),4.25-4.40 (m 1H), 7.65 (d 1H), 8.25 (dd 1H), 8.35 (d 1H); (oil).

(d) 2-(4,4-Difluorobut-3-enylthio)-5-phenylbenzoxazole (Compound No.26). mp 41-42, 4° C.; M⁺ =317; ¹ H NMR (CDCl₃): δ 2.5-2.65 (m 2H),3.3-3.4 (t 2H), 4.25-4.45 (m 1H), 7.3-7.5 (m 5H), 7.6 (d 2H), 7.8 (s1H).

(e) 2-(4,4-Difluorobut-3-enylthio)-6-fluorobenzthiazole (Compound No15). ir 1750 cm⁻¹ ; M⁺ 275; ¹ H NMR (CDCl₃): δ 2.50(m 2H); 3.35(t 2H);4.25(m 1H); 7.10(m 1H); 7.40(dd 1H); 7.75(dd 1H); (oil).

(f) 2-(4,4-Difluorobut-3-enylthio)-4-methylbenzthiazole (Compound No16); M⁺ =271; ¹ H NMR (CDCl₃): δ 2.55(m 2H); 2.68(s 3H); 3.40(t 2H);4.32(m 1H); 7.2(m 2H); 7.60(dd 1H); (oil).

(g) 2(4,4-Difluorobut-3-enylthio)-6-methylbenzthiazole (Compound No 7).M⁺ =271; ¹ H NMR (CDCl₃): δ 2.48(s 3H); 2.55(m 2H); 3.35(t 2H);4.3(double triplet of doublets 1H); 7.20(dd 1H); 7.55(s 1H); 7.75(d 1H);(oil).

(h) 2-(4,4-difluorobut-3-enylthio)-5-methylbenzthiazole (Compound No.22). ¹ H NMR (CDCl₃): δ 7.68(1H,bs); 7.62(1H,d); 7.14(1H, bd);4.32(1H,dtd): 3.38(2H,t); 2.54(2H, bq); 2.48(3H,s); (oil).

EXAMPLE 5

A general one-step procedure for the preparation of pyrimidinessubstituted with a 4,4-difluoro-3-butenylthio group in the 2, 4 or5-position, starting with a correspondingly substitutedmercaptopyrimidine, is illustrated by the following preparation of 2-(4,4-difluoro-3-butenyl)thiol!-4-phenyl-pyrimidine (Compound No. 2.4)from 4-phenyl-2(1H)-pyrimidinethione and 4,4-difluoro-3-butenyl4-methyl-benzenesulfonate.

4-Phenyl-2(1H)-pyrimidinethione (0.29 g), 4,4-difluoro-3-butenyl4-methyl-benzene sulfonate (0.4 g), potassium carbonate (0.22 g) andpotassium iodide (catalytic amount) were mixed in acetone (20 cm³) andheated under reflux for five hours then allowed to cool overnight. Theprecipitate formed was removed by filtration and the filtrate evaporatedunder reduced pressure to give an orange solid. Chromatography on silicagel using a 90:10 mixture of hexane:ethyl acetate as eluant gaveCompound No. 2.4 as a yellow oil (0.253 g). M⁺ =278; ¹ H NMR (CDCl₃): δ2.48-2.58(2H,m); 3.28(2H,t); 4.24-4.42(1H,m); 7.38(1H,d);7.48-7.56(3H,m); 8.04-8.12(2H,m); 8.56(1H,d).

The following compounds according to the invention were prepared usingthe above procedure.

(a) 2- (4,4-difluoro-3-butenyl)thio!-4-(4-fluorophenyl)-pyrimidine(Compound No. 2.43). M⁺ =296; ¹ H NMR (CDCl₃): δ 2.46-2.58(2H,m);3.26(2H,t); 4.24-4.42(1H,m); 7.14-7.24(2H,m); 7.34(1H,d);8.04-8.14(2H,m); 8.54(1H,d); (off-white solid mp 44-45° C.).

(b) 4-cyclopropyl-2- (4,4-difluoro-3-butenyl)thio!-pyrimidine (CompoundNo. 2.46). M⁺ =242; ¹ H NMR (CDCl₃): δ 1.02-1.20(4H,m); 1.84-1.98(1H,m);2.34-2.48(2H,m); 3.10(2H,t); 4.18-4.38(1H,m); 6.82(1H,d); 8.26(1H,d);(oil)

(c) 2- (4,4-difluoro-3-butenyl)thio!-4-(1-methylcyclopropyl)-pyrimidine(Compound No. 2.47). M⁺ =256; ¹ H NMR (CDCl₃): δ 0.88-0.94(2H,m);1.32-1.38(2H,m); 1.48(3H,s); 2.36-2.48(2H,m); 3.10(2H,t);4.20-4.38(1H,m); 6.94(1H,d); 8.34(1H,d); (oil).

EXAMPLE 6

This Example illustrates the preparation of4-bromo-1,1-difluorobut-1-ene.

(a) Preparation of 1,4-dibromo-1,1,2-trifluorobutane.

Commercially available 4-bromo-1,1,2-trifluorobut-1-ene (240 g, 1.27mol) was washed with water (300 ml) and then with brine (300 ml) anddried (MgSO₄) before use. Benzoyl peroxide (ca. 0.7 g) was added in oneportion, and hydrogen bromide gas was bubbled through the mixture atsuch a rate that the reaction temperature was maintained at between 30to 40° C. After 2 hours, gas chromatography of a sample of the reactionmixture showed that little starting material remained. The reactionmixture was washed with water (300 ml), then with saturated sodiumbicarbonate solution, and then again with water (300 ml) dried (MgSO₄)and filtered to give a pale yellow oil (296.7 g, 87%) identified as1,4-dibromo-1,1,2-trifluorobutane. Proton NMR (CDCl₃ solution): δ2.38(2H,m,BrCH₂ CH₂), 3.57(2H,m,BrCH₂ CH₂), and 4.90 (H, m,CHFCF₂ Br).Gas chromatographic analysis showed that the product was more than 98%pure.

(b) Preparation of 4-bromo-1,1-difluorobut-1-ene.

Zinc powder (0.88 g) was added to a solution of1-4-dibromo-1,1,2-trifluorobutane (1.38 g) in acetone (6 ml) containingwater (one drop), under an atmosphere of nitrogen. The mixture wassubjected to ultrasonic radiation while being kept in a bath heated to55° C. After 45 minutes, gas chromatographic analysis showed that alarge proportion of the dibromobutane had been consumed. The mixture wasthen added to more zinc powder (3 g) in acetone containing a trace ofwater, which had been pre-heated to 55° C. After a further 20 minutes atthis temperature, gas chromatographic analysis of a sample of thereaction mixture indicated that all of the dibromobutane startingmaterial had been consumed, showing that the de-bromofluorinationreaction had initiated. More 1,4-dibromo-1,1,2-trifluorobutane (12.34 g)was then added to the reaction mixture over a period of 75 minutes whilethe reaction mixture was kept at 55° C. Heating was then continued for afurther 95 minutes. Gas chromatographic analysis of a sample indicatedthat about 3% of the dibromobutane remained unchanged. Further zincpowder (0.16 g) was added and heating continued until gc analysis showedthat the dibromobutane had been completely consumed. The acetonesolution was then decanted from the zinc residues to give a solution of4-bromo-1,1-difluorobut-1-ene suitable for use in further chemicalreactions.

EXAMPLE 7

This Example illustrates the preparation of2-(4,4-difluorobut-3-enyl)thiobenzthiazole and2-(4,4-difluorobut-3-enyl)thiobenzoxazole according to the invention.

To the solution of 4-bromo-1,1-difluorobut-1-ene prepared in Example 6was added potassium carbonate (10.76 g) and 2-mercaptobenzthiazole (9.18g). The mixture was stirred at 55° C. for 6 hours and then at roomtemperature overnight. Gas-liquid chromatography of a sample of thereaction mixture showed that a small amount of4-bromo-1,1-difluorobut-1-ene remained. More potassium carbonate (1.0 g)was added and the mixture heated for another two and a half hours at 55°C., when all of the bromo compound had been consumed. The mixture wascooled to room temperature and filtered. The residue was washed withacetone and the filtrate and washings combined and evaporated underreduced pressure to give the crude product (16.18 g). This was dissolvedin dichloromethane. The solution was filtered and washed with dilutesodium hydroxide (2×25 ml) and with brine (2×25 ml), dried overmagnesium sulphate, filtered, the filtrate evaporated to give2-(4,4-difluorobut-3-enyl)thiobenzthiazole, having a gas chromatographicretention time identical with that of an authentic sample. The yield was63% based on the quantity of 1,4-dibromo-1,1,2-trifluorobutane used instep (b) of Example 1. 2-(4,4-Difluorobut-3-enyl)thiobenzoxazole wasprepared in the same way, but using 2-mercapto benzoxazole instead of2-mercapto benzthiazole.

EXAMPLE 8

This Example further illustrates the preparation of4-bromo-1,1-difluorobut-1-ene, by debromofluorination of1,4-dibromo-1,1,2-trifluorobutane. In this example, catalytic amounts ofiodine and zinc iodide were used to initiate the debromofluorinationreaction, rather than irradiation with ultra-sound as in Example 6.

1,4-Dibromo-1,1,2-trifluorobutane (8.05 g, 30 mmol) in methanol (3 ml,dried by molecular sieve and purged with nitrogen) was added dropwiseover a period of 90 minutes to a mixture of zinc dust (3 g, 1.5 eq., 45mmol), iodine (catalytic amount), zinc iodide (catalytic amount), andmethanol (10 ml dried by molecular sieve) under a nitrogen atmosphere atroom temperature. The reaction mixture was stirred for a further 10minutes after addition was complete, and then filtered through a smallbed of silica. Water (20 ml) was added to the filtrate and the organiclayer separated (2.65 g, 53%). The organic layer was distilled in aKugelrohr apparatus (Buchi GKR-51) at an oven temperature of 90° C. togive a clear oil identified as 4-bromo-1,1-difluorobut-1-ene. ProtonNMR: δ 2.56(2H,q,CH₂ CH2Br), 3.4(2H,t,CH₂ CH₂ Br), and 4.3(1H,dt,CF₂═CH)

EXAMPLE 9

This Example illustrates the preparation of 4-(4,4-difluoro-3-butenyl)thio!-pyrimidine. 4-Bromo-1,1-difluorobut-1-ene(1.86 g), 4(3H)pyrimidinethione (1.12 g), potassium carbonate (5 g) andacetone (60 ml) is heated and stirred under reflux for 5 hours, cooled,and filtered. The filtrate is evaporated and the residue chromatographedon silica gel using a mixture of ethyl acetate and hexane as eluent togive 4- (4,4-difluoro-3-butenyl)thio!-pyrimidine as an oil.

EXAMPLE 10

This Example illustrates the preparation of4-bromo-1,1-difluorobut-1-ene in water as the reaction medium.

Zinc powder (98 g) was stirred in water (400 ml) and iodine (0.6 g) wasadded as a catalyst. Stirring was continued and the slurry was heated to80-85° C. under an atmosphere of nitrogen.1,4-Dibromo-1,1,2-trifluorobutane (281.5 g) was added dropwise over aperiod of 2.5 hours. After addition was complete, heating was continuedfor a further 2.5 hours, when gas-liquid chromatography confirmed thatall of the starting material had been consumed. The product,4-bromo-1,1-difluorobut-1-ene, was distilled from the reaction mixture.The bulk of the product was collected at a head temperature of 77.3° C.The product was collected up to a head temperature of 100° C.

The yield of product was 132.2 g, having a purity of 94% as measured bygc.

EXAMPLE 11

This Example illustrates the preparation of4-bromo-1,1-difluorobut-1-ene by electrochemical dehalogenation of1,4-dibromo-1,1,2-trifluorobutane.

A solution of zinc chloride (2.0 g) in de-ionised water (40 ml) wascharged to the cathode compartment of a small laboratory scaleelectrolyte cell. Some of the solution was allowed to diffuse throughglass frit cell divider (30 mm diameter) and into the anode compartment.The cathode consisted of a lead disc (diameter 25 mm) mounted parallelto and 25 mm away from the cell divider. The anode consisted of a singlegraphite rod, 12 mm in diameter. 1,4-Dibromo-1,1,2-trifluorobutane (5.0g) was charged to the cathode compartment, which was stirred with amagnetic stirring bar. A little surface-active agent was added to assistin dispersing the 1,4-dibromo-1,1,2-trifluorobutane. A current of 1.0amp was passed through the cell for 2 hours, when gc analysis showedthat only 2% of untreated starting material remained. The contents ofthe cathode compartment were distilled and the distillate collected upto a head temperature of 100° C. The yield of4-bromo-1,1-difluoro-but-1-ene, identified by its NMR spectrum, was 1.4g.

EXAMPLE 12

This Example illustrates the preparation of4-bromo-1,1-difluorobut-1-ene by dehalogenation of1,4-dibromo-1,1,2-trifluorobutane with aluminium metal using water asthe reaction medium.

Aluminium powder (0.4 g) was suspended in water (10 ml), and a crystalof iodine and concentrated hydrochloric acid (3 drops) were added.1,4-Dibromo-1,1,2-trifluorobutane (270 g) was added, and the mixturestirred at room temperature until the colour of the iodine wasdischarged. The reaction mixture was then heated to 67° C. overnight (18hours) with stirring, when gc analysis showed that only 2% of untreatedstarting material remained. The product was distilled from the reactionmixture and the distillate passing over at between 65° C. and 100° C.was collected. The yield of 4-bromo-1,1-difluorobut-1-ene was 0.74 g.

This was analysed by gc and found to be 83.7% pure. The identity of theproduct was confirmed by NMR. ##STR1##

We claim:
 1. A compound of formula IX:

    CF.sub.2 BrCHFCH.sub.2 CH.sub.2 OSO.sub.2 R.sup.a          IX:

wherein R^(a) is C₁₋₄ alkyl or phenyl optionally substituted by C₁₋₄alkyl.
 2. A process for preparing 4-bromo-1,1-difluoro-but-1-ene whichcomprises treating 1,4-dibromo-1,1,2-trifluorobutane with adebromofluorinating agent.
 3. A process as claimed in claim 2 whereinthe debromofluorination reaction is carried out in a reaction mediumconsisting essentially of water.